Glycolytic enzymes can modulate cellular life span.

By H. Kondoh, M. Lleonart, Jesús Gil, Jing Wang, P. Degan, G. Peters, Dolores Martínez, A. Carnero, D. Beach. Cancer Research, 2005

661 citations recorded by the source corpus.

An unbiased screen for genes that can immortalize mouse embryonic fibroblasts identified the glycolytic enzyme phosphoglycerate mutase (PGM). A 2-fold increase in PGM activity enhances glycolytic flux, allows indefinite proliferation, and renders cells resistant to ras-induced arrest. Glucosephosphate isomerase, another glycolytic enzyme, displays similar activity and, conversely, depletion of PGM or glucosephosphate isomerase with short interfering RNA triggers premature senescence. Immortalized mouse embryonic fibroblasts and mouse embryonic stem cells display higher glycolytic flux and more resistance to oxidative damage than senescent cells. Because wild-type p53 down-regulates PGM, mutation of p53 can facilitate immortalization via effects on PGM levels and glycolysis.

Subfields: Oncology, Physiology, Surgery

View Paper: https://www.semanticscholar.org/paper/3533acdd3761c694734daf0fd88d67e041d3e400

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Citations in the corpus

Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species (2010, background): “For example, p53 decreases the glycolytic rate through inhibiting expression of glucose transporters (6) and phosphoglycerate mutase (7) while increasing the expression of TIGAR that reduces fructose-2,6-bisphosphate levels (8).”
HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. (2013, positive): “Notably, depletion of glucosephosphate isomerase (GPI) or phosphoglycerate mutase 1 (PGAM1) (Figure 3) by RNA interference also induces senescence (60), indicating the critical role of glucose metabolism in maintaining proliferation.”
ROS and p53: a versatile partnership. (2008, background): “expression of PGM, thus inhibiting the glycolytic pathway and promoting respiration and ROS formation [42].”
p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase (2011, background): “Recent studies indicated that p53 also has a role in modulating metabolism including glycolysis and oxidative phosphorylatio”
Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer (2009, background): “The tumour suppressor p53 has been shown to decrease the activity of glycolytic enzymes such as phosphoglycerate mutase [70] and to inhibit glycolysis through the induction of TIGAR, a regulatory protein for p53-induced glycolysis and apoptosis that modulates the levels of fructose-2, 6-bisphosphate”
p53 in health and disease (2007, background): “Regulation of glycolysis by p53 can also affect cellular, and so potentially organismal, lifespa”
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate (2012, background): “In tumors, the loss of p53 can enhance glycolysis and anabolic synthesis from glycolytic intermediates (Bensaad et al., 2006; Kondoh et al., 2005; Matoba et al., 2006).”
Blinded by the Light: The Growing Complexity of p53. (2009, background): “, 2008), dampening glycolysis (Bensaad et al., 2006; Kondoh et al., 2005), and enhancing mitochondrial respiration (Ma et al.”
HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. (2007, background): “Expression of two other glycolytic enzymes, phosphoglycerate mutase and glucose phosphate isomerase, was shown to immortalize primary human cells and attenuate the mitochondrial generation of ROS, which are known to cause cellular senescence (Kondoh et al., 2005).”
Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review). (2012, background): “Moreover, mutant p53 also increases the activity of two other glycolytic enzymes, HK2 and phosphoglycerate mutase (PGM), catalyzing 3-phosphoglycerate (3PG) to 2-phosphoglycerate (2PG) (71,73,79).”
p53 regulates glucose metabolism through an IKK-NF-κB pathway and inhibits cell transformation (2008, background): “It has been reported that p53 activation causes downregulation of several glycolysis-regulating factors such as the glycolytic enzyme phosphoglycerate mutase (PGM”
Tumor cell metabolism: cancer's Achilles' heel. (2008, background): “…of the protein synthesis of cytochrome c oxidase 2 (SCO2), which is required for assembling COX (Matoba et al., 2006). p53 negatively regulates phosphoglycerate mutase (PGM), the enzyme that converts 3-phosphoglycerate (3PG) to 2-phosphoglycerate (2PG) in glycolysis (Kondoh et al., 2005).”
Metabolic Plasticity in Stem Cell Homeostasis and Differentiation (2012, positive): “Indeed, increased expression of glycolytic enzymes and stimulation of glycolysis is required for cell immortalization and is sufficient to increase cellular lifespan (Kondoh et al., 2005).”